Trial Outcomes & Findings for Effect of Modulating Gamma Oscillations Using tACS (NCT NCT03412604)

Last Updated: 2022-08-22

Results Overview

Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions. The metric used is standardized uptake value ratio (SUVR), a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.

Recruitment status

COMPLETED

Study phase

Target enrollment

5 participants

Primary outcome timeframe

baseline and up to 12 weeks

Results posted on

2022-08-22

Participant Flow

5 participants were enrolled in the study. 4 out of 5 participants completed the study. 1 study subject did not complete the follow-up amyloid and tau PET scans.

Participant milestones

Participant milestones
Measure	tACS Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Transcranial Alternating Current Stimulation (tACS): tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
Overall Study STARTED	5
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	tACS Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Transcranial Alternating Current Stimulation (tACS): tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Effect of Modulating Gamma Oscillations Using tACS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	tACS n=5 Participants Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Transcranial Alternating Current Stimulation (tACS): tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
Age, Customized 56	1 Participants n=5 Participants
Age, Customized 64	1 Participants n=5 Participants
Age, Customized 73	1 Participants n=5 Participants
Age, Customized 84	2 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and up to 12 weeks

Outcome measures

Outcome measures
Measure	tACS n=5 Participants Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Transcranial Alternating Current Stimulation (tACS): tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
PET Amyloid Burden	-1.11 SUVR Standard Deviation 0.76

PRIMARY outcome

Timeframe: up to 12 weeks

Changes in the tau deposition observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions. The metric used is SUVR, a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR (dSUVR) for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.

Outcome measures

Outcome measures
Measure	tACS n=5 Participants Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Transcranial Alternating Current Stimulation (tACS): tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
PET Tau Deposition	-2.85 SUVR Standard Deviation 1.20

SECONDARY outcome

Timeframe: up to 12 weeks

Changes in the microglia activation observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions. The metric used is SUVR, a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR (dSUVR) for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.

Outcome measures

Outcome measures
Measure	tACS n=5 Participants Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Transcranial Alternating Current Stimulation (tACS): tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
PET Microglia Activation	-0.56 SUVR Standard Deviation 1.08

SECONDARY outcome

Timeframe: 6 weeks (pre-post tACS intervention)

Patients underwent a comprehensive MRI exam before and after the tACS intervention, including measures of brain perfusion via Arterial Spin Labeling (ASL) sequences. The outcome measure represent the average change in perfusion (i.e. blood flow) recorded in regions targeted by tACS. Since Alzheimer's Disease is also characterized by a decrease of brain metabolism, an increased of blood flow after treatment would constitute a very promising sign of tACS efficacy in reducing Alzheimer's pathology in the brain. We will report the change in blood flow (mean, standard deviation) after tACS treatment.

Outcome measures

Outcome measures
Measure	tACS n=5 Participants Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Transcranial Alternating Current Stimulation (tACS): tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
Changes in Brain Perfusion as Measured by Arterial Spin Labeling	1.2 mg/min/100gr Standard Deviation 0.6

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 12 weeks

Change in Adas-Cog score will be reported, to document a potential clinical benefit of tACS. The scale ranges from 0-70 with higher score indicating greater cognitive impairment.

Outcome measures

Outcome measures
Measure	tACS n=5 Participants Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Transcranial Alternating Current Stimulation (tACS): tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
Alzheimer's Disease Assessment Scale -Cog Score	1.5 Scores on a scale Standard Deviation 2.9

Adverse Events

tACS

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	tACS n=5 participants at risk Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Transcranial Alternating Current Stimulation (tACS): tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
General disorders Sensation Under Electrodes	20.0% 1/5 • Number of events 1 • 1 year

Other adverse events

Other adverse events
Measure	tACS n=5 participants at risk Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Transcranial Alternating Current Stimulation (tACS): tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
General disorders Headache	20.0% 1/5 • 1 year
General disorders Scalp Pain	40.0% 2/5 • 1 year
General disorders Neck Pain	20.0% 1/5 • 1 year
General disorders Skin Irritation	60.0% 3/5 • 1 year
General disorders Sensations Under Electrodes	100.0% 5/5 • 1 year
General disorders Visual Changes	60.0% 3/5 • 1 year
General disorders Mood Change	20.0% 1/5 • 1 year

Additional Information

Emiliano Santarnecchi

Massachusetts General Hospital

Phone: 617-667-0326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place